Biology subjects

Gourmet, L. E.

Publications and source records attributed to Gourmet, L. E..

2 recordsLinked to original sources

bioRxiv2024

Examination of the role of mutualism in immune evasion

Though the earliest stages of oncogenesis, post initiation, are not well understood, it is generally appreciated that a successful transition from a collection of dysregulated cells to an aggressive tumor requires complex ecological interactions between cancer cells and their environment. One key component of tumorigenesis is immune evasion. To investigate the interplay amongst the ecological behaviour of mutualism and immune evasion, we used a computational simulation framework. Sensitivity analyses of the growth of a virtual tumor implemented as a 2D-hexagonal lattice model suggests tumor survival depends on the interplay between growth rates, mutualism and immune evasion. In 60% of simulations, cancer clones with low growth rates, but exhibiting mutualism were able to evade the immune system and continue progressing suggesting that tumors with equivalent growth rates and no mutualism are more likely to be eliminated than tumors with mutualism. Tumors with faster growth rates showed a lower dependence upon mutualism for progression. Geostatistical analysis showed decreased spatial heterogeneity over time for polyclonal tumours with a high division rate. Overall, these results suggest that in slow growing tumors, mutualism is critical for early tumorigenesis.

bioinformatics↗

bioRxiv2021

Genomic hallmarks of cellular dormancy in cancer and therapeutic implications

Therapy resistance in cancer is often driven by a subpopulation of cells that are temporarily arrested in a non-proliferative G0 state, which is difficult to capture and whose mutational drivers remain largely unknown. We developed methodology to robustly identify this state from transcriptomic signals and characterised its prevalence and genomic constraints in solid primary tumours. We show that G0 arrest preferentially emerges in the context of more stable, less mutated genomes which maintain TP53 integrity and lack the hallmarks of DNA damage repair deficiency, while presenting increased APOBEC mutagenesis. We employ machine learning to uncover novel genomic dependencies of this process and validate the role of the centrosomal gene CEP89 as a modulator of proliferation/G0 arrest capacity. Lastly, we demonstrate that G0 arrest underlies unfavourable responses to various therapies exploiting cell cycle, kinase signalling and epigenetic mechanisms in single cell data, and propose a G0 arrest transcriptional signature that is linked with therapeutic resistance and can be used to further study and clinically track this state.

cancer biology↗